Variations among species and cell types in the effects of caffeine on mutagen-induced cytotoxicity and postreplication repair of DNA.
The influence of caffeine on cytotoxicity and postreplication repair of DNA was examined following exposure of several cell types to physical and chemical agents known to damage DNA. The cell types used in this study were normal human fibroblasts (HS-WP), human xeroderma pigmentosum fibroblasts (SGL), Chinese hamster V79 cells, mouse BALB/c-3T3 cells, and secondary Syrian hamster embryo cells. The DNA damaging agents were ultraviolet light (UV), N-2-acetoxy-fluorenylacetamide (AFAA), nitroquinoline-N-oxide (NQO) and N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Induction of cytotoxicity in Chinese hamster V79 cells due to ultraviolet light or AFAA exposure was enhanced by caffeine at a concentration of 1.0 mM in the culture medium, but not at 0.2 or 0.05 mM. Caffeine also inhibited postreplication repair in these cells at the same concentrations. In contrast, postreplication repair was not affected by caffeine at concentrations up to 1.0 mM in normal human fibroblasts (HS-WP), human xeroderma pigmentosum fibroblasts (SGL), secondary Syrian hamster embryo cells, and mouse BALB/c-3T3 cells following treatment with ultraviolet light, AFAA, NQO, or MNNG. Cytotoxicity in BALB/c-3T3 cells following exposure to ultraviolet light or AFAA was enhanced in the presence of caffeine at 1.0 or 0.2 mM, although these concentrations of caffeine had no effect on postreplication repair in these cells. The inhibitory effect of caffeine on postreplication repair was found only in Chinese hamster V79 cells among the five cell types used in this study. Both normal and xeroderma pigmentosum human cells repaired mutagen-induced DNA damage equally well in the absence or presence of caffeine at concentrations of 1.0 mM or less.
D015073:2-Acetylaminofluorene / Q000494:pharmacology; D015112:4-Nitroquinoline-1-oxide / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006224:Cricetinae; D003412:Cricetulus; D004260:DNA Repair / Q000187:drug effects* / Q000528:radiation effects; D004357:Drug Synergism; D004622:Embryo, Mammalian; D005347:Fibroblasts; D006801:Humans; D008647:Mesocricetus; D008769:Methylnitronitrosoguanidine / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D009153:Mutagens / Q000494:pharmacology*; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum
D009153:Mutagens; D008769:Methylnitronitrosoguanidine; D002110:Caffeine; D015112:4-Nitroquinoline-1-oxide; D015073:2-Acetylaminofluorene